Several molecular genetic studies have been conducted by our laboratory staff over the past year. A collaboration with epidemiologists at the NCI was initiated to study the interaction between molecular and classical risk factors of oral cancer. We are using biological samples already collected in a case-control study of oral and pharyngeal cancer conducted in Puerto Rico. The study focused on Puerto Rico because of the especially high incidence of oral cancer known to occur there. A second molecular epidemiological study of oral cancer is being conducted in Athens, Greece, in collaboration with Dr. Anthanasios Zavras, a dentist and Ph.D. student in the Department of Oral Health Policy and Epidemiology at School of Dental Medicine, Harvard University. We are using a case-control design, based on recruitment in hospitals in Athens. Our laboratory's role is to perform the molecular and statistical analyses for this study, as well as provide guidance about the study's design and performance. Risk factors, family histories of cancer and biological samples (oral rinses and brushings, tumor biopsy or surgical specimens (if available) and blood spots on filter paper) are being delivered to our laboratory for patients and controls. We have begun to evaluate genes potentially responsible for oral cancer, such as those of the cytochrome P450 pathway and in a preliminary analysis found a lack of association with the CYP1A1 gene in this population. In addition, three inter-related studies of oral cancer genetic epidemiology were conducted in Taiwan during the past year. These studies were aimed at determining the basic causes of this disease. We have studied a case-control sample and found an association between genetic variation at the cytochrome P450 gene 1A1 which interacts with exposure to risk factors such as smoking and drinking.